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. 1969 Sep 1;130(3):505–518. doi: 10.1084/jem.130.3.505

C3 LEUKOTACTIC FACTORS PRODUCED BY A TISSUE PROTEASE

Jeffrey H Hill 1, Peter A Ward 1
PMCID: PMC2138703  PMID: 4185247

Abstract

When various rat tissues are incubated in homologous serum, a factor chemotactic in vitro for neutrophils is generated. The amount of chemotactic activity is a function of duration of incubation and the quantity of heart tissue or serum employed. Addition of trypsin inhibitor or antibody to the third component of complement (C3) precludes generation of chemotactic activity. In addition, antibody to C3 ablates chemotactic activity even after its formation. Purified human C3 (β1C-globulin) effectively substitutes for serum in the generation of chemotactic activity by heart tissue. The active product, as determined by gel filtration or by ultracentrifugal analysis in a sucrose density gradient, appears to be a cleavage product of C3 with a molecular weight of approximately 14,000. In addition, a larger C3 fragmentation product varying in molecular weight, depending upon experimental conditions, is also found. The protease in rat heart tissue capable of cleaving C3 into chemotactic fragments is a serine esterase with trypsin-like properties and can be inhibited by organophophorous compounds or trypsin inhibitors. The use of amino acid esters in the manner of competitive substrate inhibition confirms the trypsin-like nature of the protease. The presence of a protease in heart, and presumably in other normal tissues, capable of fragmenting C3 into factors with chemotactic activities may explain the development of the acute inflammatory response when tissues are non-specifically injured. If true, this would reinforce the role of the complement system in the mediation of nonimmunologically induced inflammation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andrews P. The gel-filtration behaviour of proteins related to their molecular weights over a wide range. Biochem J. 1965 Sep;96(3):595–606. doi: 10.1042/bj0960595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Becker E. L., Ward P. A. Partial biochemical characterization of the activated esterase required in the complement-dependent chemotaxis of rabbit polymorphonuclear leukocytes. J Exp Med. 1967 Jun 1;125(6):1021–1030. doi: 10.1084/jem.125.6.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bokisch V. A., Müller-Eberhard H. J., Cochrane C. G. Isolation of a fragment (C3a) of the third component of human complement containing anaphylatoxin and chemotactic activity and description of an anaphylatoxin inactivator of human serum. J Exp Med. 1969 May 1;129(5):1109–1130. doi: 10.1084/jem.129.5.1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cochrane C. G., Müller-Eberhard H. J. The derivation of two distinct anaphylatoxin activities from the third and fifth components of human complement. J Exp Med. 1968 Feb 1;127(2):371–386. doi: 10.1084/jem.127.2.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dalmasso A. P., Müller-Eberhard H. J. Hemolytic activity of lipoprotein-depleted serum and the effect of certain anions on complement. J Immunol. 1966 Nov;97(5):680–685. [PubMed] [Google Scholar]
  6. HURLEY J. V. SUBSTANCES PROMOTING LEUKOCYTE EMIGRATION. Ann N Y Acad Sci. 1964 Aug 27;116:918–935. doi: 10.1111/j.1749-6632.1964.tb52558.x. [DOI] [PubMed] [Google Scholar]
  7. Jensen J. Anaphylatoxin in its relation to the complement system. Science. 1967 Mar 3;155(3766):1122–1123. doi: 10.1126/science.155.3766.1122. [DOI] [PubMed] [Google Scholar]
  8. KWAAN H. C., ASTRUP T. LOCALIZATION OF FIBRINOLYTIC ACTIVITY IN MYOCARDIAL INFARCTS IN RATS. Thromb Diath Haemorrh. 1964 Dec 31;12:407–417. [PubMed] [Google Scholar]
  9. NILSSON U. R., MUELLER-EBERHARD H. J. ISOLATION OF BETA IF-GLOBULIN FROM HUMAN SERUM AND ITS CHARACTERIZATION AS THE FIFTH COMPONENT OF COMPLEMENT. J Exp Med. 1965 Aug 1;122:277–298. doi: 10.1084/jem.122.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Shin H. S., Snyderman R., Friedman E., Mellors A., Mayer M. M. Chemotactic and anaphylatoxic fragment cleaved from the fifth component of guinea pig complement. Science. 1968 Oct 18;162(3851):361–363. doi: 10.1126/science.162.3851.361. [DOI] [PubMed] [Google Scholar]
  11. Snyderman R., Gewurz H., Mergenhagen S. E. Interactions of the complement system with endotoxic lipopolysaccharide. Generation of a factor chemotactic for polymorphonuclear leukocytes. J Exp Med. 1968 Aug 1;128(2):259–275. doi: 10.1084/jem.128.2.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. WARD P. A., COCHRANE C. G. BOUND COMPLEMENT AND IMMUNOLOGIC INJURY OF BLOOD VESSELS. J Exp Med. 1965 Feb 1;121:215–234. doi: 10.1084/jem.121.2.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. WARD P. A., COCHRANE C. G., MUELLER-EBERHARD H. J. THE ROLE OF SERUM COMPLEMENT IN CHEMOTAXIS OF LEUKOCYTES IN VITRO. J Exp Med. 1965 Aug 1;122:327–346. doi: 10.1084/jem.122.2.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ward P. A. A plasmin-split fragment of C'3 as a new chemotactic factor. J Exp Med. 1967 Aug 1;126(2):189–206. doi: 10.1084/jem.126.2.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ward P. A., Cochrane C. G., Muller-Eberhard H. J. Further studies on the chemotactic factor of complement and its formation in vivo. Immunology. 1966 Aug;11(2):141–153. [PMC free article] [PubMed] [Google Scholar]

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